Study on Early Brain Injury Mechanism and Comprehensive Intervention of VCI

Alzheimer\'s disease (AD) and vascular dementia (VaD) are the most common forms of senile dementia. Although the animal research of dementia has made remarkable progress, clinical trials of drugs for AD pathology have failed in recent years. The study of dementia based on cell and animal model generally aims at a single mechanism and target, and its results are quite different from the real clinical environment. More and more studies suggest that investigators should shift the focus of research to the early stage of cognitive impairment before dementia. Prevention is more important than cure, and intervention against multi-factors and multi-targets has become an important consensus. A large number of studies have shown that the mechanism of vascular brain injury plays an important role in the pathogenesis of AD and VaD, and many vascular risk factors are interventionable to some extent. Therefore, based on the clinical cohort, in-depth study of vascular cognitive impairment (Vascular cognitive impairment, VCI) has important clinical significance for the effective prevention and treatment of AD and VaD. The leading team of the project has focused on VCI research for a long time. After nearly 20 years of experimental research and preliminary clinical observation, it is proposed that chronic cerebral ischemia can not only be a clinical disease entity, but also an important pathological basis for the early onset of VCI. This view has recently been supported by a number of authoritative international research evidence. Big data\'s study of 1171 patients with AD reported by Nature Commun in 2016 shows that the early pathological changes of AD may not be a cascade of amyloid protein (Aβ), but a decrease in cerebral blood flow. Therefore, this project intends to establish an early clinical research cohort of VCI to focus on three key issues in VCI research and clinical practice: (1) the theory that cerebral hypoperfusion may be an important pathological basis for the occurrence and development of VCI needs direct evidence support from clinical studies, and its mechanism needs further elucidation. (2) Based on the fusion of multimodal MRI of VCI vascular brain injury pathology and PET imaging markers of Aβ molecular pathology, a multivariate VCI cognitive evaluation model is constructed, and its sensitivity and specificity may be better than the existing VCI diagnostic standards. (3) the protective effect of early comprehensive intervention of vascular risk factors on cognitive decline in VCI may be more effective than that of single risk factor. The first part of this project is to establish a study cohort of non-demented vascular cognitive impairment(VCIND). Neurocognitive function assessment combined with multimodal MRI including ASL, DCE, DTI and BOLD techniques were used to observe the role of cerebral hypoperfusion in the early stage and progression of VCI. At the same time, the relationship between the changes of blood-brain barrier and neural network and cognitive decline was dynamically observed to verify and explore the effect and mechanism of cognitive impairment caused by cerebral hypoperfusion. The second part studies the pathology of vascular brain injury based on MRI and the molecular pathology of A β based on PET and the relationship between Aβ molecular pathology and cognitive impairment, including the main factors affecting cognitive function, and uses artificial intelligence (AI) algorithm to develop a multiple quantitative evaluation system of VCI cognitive function, which is mainly based on the fusion of MRI and PET image markers. In the third part, a multicenter randomized controlled clinical cohort study was conducted to observe the cognitive protective effect of comprehensive intensive intervention of vascular risk factors on early VCI, so as to provide direct clinical evidence and intervention model for the prevention and treatment of VCI. The topics of the above three aspects covered by this project are closely related, which is not only a key scientific problem, but also an important clinical problem to be solved in the diagnosis and treatment of VCI. The study of this project is expected to further clarify the role and mechanism of cerebral hypoperfusion in VCI, provide a new theoretical basis for the prevention and treatment of dementia, and develop a quantitative evaluation system of VCI cognitive function mainly based on imaging technology and AI algorithm, so as to provide a more accurate and convenient diagnostic tool for early clinical identification and scientific research of VCI. Draw up the early comprehensive intervention paradigm of VCI based on vascular risk factors and popularize it in clinic, gradually form an expert consensus, enrich and update the guidelines for diagnosis and treatment of dementia, and effectively improve the level of prevention and treatment of dementia related to VCI.